Plasma Concentration of Cystatin-C and Mannose Binding Protein and the Risk of Developing Peripheral Vascular Disease
Background- Cystatin-C, a cysteine protease inhibitor, and mannose binding lectin, an innate defense protein involved in microbial clearance, have both been hypothesized to mediate atherosclerotic plaque progression. However, little prospective data are available evaluating whether levels of these proteins in healthy individuals are associated with incident cardiovascular disease. Methods and Results-Employing a prospective, nested, case control study design, baseline levels of cystatin-C and mannose binding protein were evaluated among 133 apparently healthy men who subsequently developed symptomatic peripheral arterial disease (cases) and among 133 age and smoking matched controls who remained free of reported vascular disease during a 5 year follow-up period. Overall, median baseline levels of cystatin-C were virtually identical among case and control subjects (0.83mg/L, p=0.84). Similarly, median baseline levels of mannose binding protein among cases and controls were 2.32mg/L and 2.2mg/L,(p=0.69). We found no evidence of association between either cystatin-C or mannose binding protein and the development of peripheral vascular disease in analyses evaluating for linear trends or for threshold effects (all p values >0.05). Conclusion-In contrast to prior retrospective and cross-sectional studies, we found no evidence in this prospective evaluation that baseline levels of cystatin-C or mannose binding protein are associated with increased risk of future vascular disease.